Glutathione (GSH) is important in both differentiation of the blastocyst and protection of its cells from toxicants. This proposal investigates the hypothesis that the preimplantation embryo is sensitive to toxicants that perturb GSH status and GSH plays a critical role in regulation of apoptosis in the blastocyst. A potential relationship to embryonic death or birth defects is suggested. This proposal will address 1) the role of the maternal reproductive tract in the regulation of embryonic GSH and protection from GSH depleting toxicants; 2) the role of GSH and reactive oxygen species in the regulation of apoptosis in cells of the blastocyst and the potential for toxicant disruption of apoptosis; and 3) examine the effects of selected toxicants that deplete GSH on embryo development. Preimplantation mouse embryos will be exposed in vivo and in vitro to GSH-depleting chemicals, and GSH status, cellular apoptosis, embryonic death, and pup malformations will be monitored. The results of these studies could aid in understanding whether exposure of preimplantation embryos to environmental toxicants is a major cause of embryonic death or birth defects.